This application is for a five-year renewal of the Alzheimer's Disease Research Center (ADRC) at the University of Kentucky's Sanders-Brown Center on Aging. The UK ADRC has developed a multi-disciplinary program including basic and clinical research, exemplary clinical care and neuropathological activities, satellite clinics for rural and minority subjects and a broad spectrum of educational training programs, all of which are responsive to investigators, health care delivery professionals, AD families and needs of the community, state and region. The long-term objective is to a) build on our established broad based AD program, b) enhance our understanding of the early clinical and neuropathological manifestations of AD through study of our unique community-based normal aged control group and c) study the pathogenetic mechanisms of neuron degeneration with the eventual goals goal of preventing the disease. The ADRC is house in a building in a building dedicated to aging and AD research which has had 20 new laboratories added this year. The application consists of five core and four projects. The Administrative Core organizes, coordinates and supervises all ADRC activities. The Biostatistical and Data Management Cores maintain and manage data sets from the Cores and provides valuable assistance in experimental design and statistical analysis. The Clinical Core evaluates and longitudinally follows AD patients and our unique normal aged control group. It maintains satellite diagnostic and treatment clinics for underserved, rural subjects in Appalachian eastern Kentucky and African-American subjects in conjunction with Meharry Medical School in Nashville, TN. The Neuropathology Core provides a Rapid Autopsy Program that performs short postmortem interval autopsies on AD patients and normal control subjects and maintains a brain bank. The Education and autopsies on AD patients and normal control subjects and maintains a brain bank. The Education and Information Transfer Core provides training for investigators and disseminate information to health care professionals, caregivers and the lay public. The research projects in this renewal request includes, "Mechanisms of synapse degeneration" (Project 1, Dr. Mattson); "Recovery from Cytoskeletal Disruption" (Project 2, Dr. Geddes); "Novel Peptide Inhibitors of Abeta accumulation and action" (Project 3, Dr. Estus), and "Lipid peroxidation, antioxidants in AD" (Project 4, D. Montine). Pilot studies will be determined annually.